Ensuring stability of pharmaceutical agents within dosage forms that include suspensions is important, for example, for effective dosaging and/or shelf-stability. Pharmaceutical suspensions can be used, for example, in osmotic drug delivery devices and injection depot devices. Osmotically-driven, also referred to as pump-driven, devices include those described in U.S. Pat. Nos. 5,985,305; 6,113,938; 6,132,420; 6,156,331; 6,395,292; each of which is incorporated herein by reference.
One approach to providing a stable suspension of a pharmaceutical agent is to provide a dosage form containing a suspending vehicle whose viscosity is sufficiently high to slow the sedimentation rate of the pharmaceutical agent. Typically, suspending vehicles contain a high viscosity, biocompatible polymer and a water-immiscible solvent. Water-immiscible solvents are typically chosen for their tendency to limit water ingress into drug dosage forms that are exposed to aqueous media, for example, bodily fluids. Such solvents have been shown to provide stable environments for pharmaceutically active agents such as proteins and peptides.
Some biocompatible polymers, such as polyvinyl pyrolidone (PVP), exhibit some amount of solubility in water. As such, some suspending vehicles separate into two phases at an organic/aqueous interface at outlets of dosage forms. Under certain conditions, suspending vehicles comprising polymer in conjunction with a water-immiscible solvent may be difficult to pump through narrow exit ports of dosage forms. Further, reliability of dosage forms can be compromised by the formation of highly viscous, almost solid formations.
Hence, there exists a need to provide suspending vehicles made of a primary component that provides a stable environment for proteins and peptides that is substantially solvent-free. Also, there is a need to eliminate pluggage of discharge ports of implantable devices. Additionally, there is a need for suspending vehicles that use a primary component which exhibit desirable suspension characteristics while at the same time remain one-phase upon contact with aqueous media.